Computed tomography-based prediction of pancreatitis following biliary metal stent placement with the convolutional neural network.

Background and study aims Pancreatitis is a potentially lethal adverse event of endoscopic transpapillary placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction (MBO). Deep learning-based image recognition has not been investigated in predicting pancreatitis in this setting. Patients and methods We included 70 patients who underwent endoscopic placement of a SEMS for nonresectable distal MBO. We constructed a convolutional neural network (CNN) model for pancreatitis prediction using a series of pre-procedure computed tomography images covering the whole pancreas (≥ 120,960 augmented images in total). We examined the additional effects of the CNN-based probabilities on the following machine learning models based on clinical parameters: logistic regression, support vector machine with a linear or RBF kernel, random forest classifier, and gradient boosting classifier. Model performance was assessed based on the area under the curve (AUC) in the receiver operating characteristic analysis, positive predictive value (PPV), accuracy, and specificity. Results The CNN model was associated with moderate levels of performance metrics: AUC, 0.67; PPV, 0.45; accuracy, 0.66; and specificity, 0.63. When added to the machine learning models, the CNN-based probabilities increased the performance metrics. The logistic regression model with the CNN-based probabilities had an AUC of 0.74, PPV of 0.85, accuracy of 0.83, and specificity of 0.96, compared with 0.72, 0.78, 0.77, and 0.96, respectively, without the probabilities. Conclusions The CNN-based model may increase predictability for pancreatitis following endoscopic placement of a biliary SEMS. Our findings support the potential of deep learning technology to improve prognostic models in pancreatobiliary therapeutic endoscopy.

Impact of temperature-controlled endobiliary radiofrequency ablation for inoperable hilar cholangiocarcinoma: A propensity score-matched analysis.

Background and study aims Endobiliary radiofrequency ablation (RFA) can be an effective palliative treatment, but few studies have evaluated its outcomes for malignant obstruction in the hilar bile duct, which has a thin wall and complex duct-vascular contacts. We evaluated the efficacy and safety of temperature-controlled endobiliary RFA, which can reduce the risk of unintentional thermal injury by maintaining the temperature of the ablation segment, in the treatment of inoperable hilar cholangiocarcinoma (CCA). Patients and methods After propensity score matching, 64 patients with inoperable hilar CCA were categorized to the RFA + stent group (endobiliary RFA with stenting; n=32) or stent-only group (stenting only; n=32). The evaluated outcomes were the median time to recurrent biliary obstruction (RBO), overall survival (OS), and adverse events (AEs). Results Technical success was achieved in all patients. The clinical success rate was 93.8% in the RFA + stent group and 87.5% in the stent-only group ( P =0.672). The median time to RBO was 242 days in the RFA + stent group and 168 days in the stent-only group ( P =0.031). The median OS showed a non-significant tendency to be higher in the RFA + stent group (337 versus 296 days; P =0.260). Overall AE rates were comparable between the two groups (12.5% vs 9.4%, P =1.000). Conclusions Temperature-controlled endobiliary RFA resulted in favorable stent patency without increasing the rate of AEs but it did not significantly increase OS in patients with inoperable hilar CCA (Clinical trial registration number: KCT0008576).

Impact of a new dedicated sheath device for tissue sampling of biliary stricture on pathological diagnostic yield: Retrospective study.

Background and study aims Endoscopic transpapillary biliary forceps biopsy (TBFB) is a common method for obtaining specimens from biliary lesions. Its diagnostic yield is unsatisfactory; to overcome this disadvantage, a dedicated sheath has been developed. This study aimed to evaluate the outcomes of conventional TBFB and TBFB with a novel sheath device. Patients and methods Consecutive patients who underwent TBFB between January 2020 and December 2021 were retrospectively evaluated. The rate of obtaining adequate samples, failed attempts at forceps insertion into the bile duct, and sensitivity were compared between the two groups. Results Ninety-two patients who underwent 115 endoscopic retrograde cholangiopancreatographies (76 in the conventional group vs. 39 in the dedicated sheath group) were included. The rates of obtaining adequate samples, failed attempts of the forceps into the bile duct, and sensitivity were 72.4% vs. 89.7% ( P = 0.03), 28.3% vs. 0% ( P < 0.01), and 66.7% vs. 88.9% ( P = 0.02), respectively. Conclusions TBFB with the novel sheath device contributed to improved sensitivity for diagnosis of biliary stricture without insertion of forceps outside the bile duct.

Per-oral cholangioscopy in patients with primary sclerosing cholangitis: a 12-month follow-up study.

Background and study aims Patients with primary sclerosing cholangitis (PSC) have a 9% to 20% lifetime incidence of cholangiocarcinoma (CCA). Per-oral cholangioscopy (POCS) added to endoscopic retrograde cholangiography (ERC) could potentially improve detection of CCA occurrence. We prospectively assessed POCS identification of 12-month CCA incidence in PSC patients undergoing ERC. Patients and methods Consecutive patients with PSC, an indication for ERC, and no prior liver transplantation were enrolled. During the index procedure, POCS preceded planned therapeutic maneuvers. The primary endpoint was ability for POCS visualization with POCS-guided biopsy to identify CCA during 12-month follow-up. Secondary endpoints included ability of ERC/cytology to identify CCA, repeat ERC, liver transplantation, and serious adverse events (SAEs). Results Of 42 patients enrolled, 36 with successful cholangioscope advancement were analyzed. Patients had a mean age 43.5±15.6 years and 61% were male. Three patients diagnosed with CCA had POCS visualization impressions of benign/suspicious/suspicious, and respective POCS-guided biopsy findings of suspicious/positive/suspicious for malignancy at the index procedure. The three CCA cases had ERC visualization impressions of benign/benign/suspicious, and respective cytology findings of atypical/atypical/suspicious for malignancy. No additional patients were diagnosed with CCA during median 11.5-month follow-up. Twenty-three repeat ERCs (5 including POCS) were performed in 14 patients. Five patients had liver transplantation, one after CCA diagnosis and four after benign cytology at the index procedure. Three patients (7.1%) had post-ERC pancreatitis. No SAEs were POCS-related. Conclusions In PSC patients, POCS visualization/biopsy and ERC/cytology each identified three cases of CCA. Some patients had a repeat procedure and none experienced POCS-related SAEs.

Provider-reported use of butylscopolamine in gastrointestinal endoscopy in Germany.

Introduction The anti-cholinergic agent hyoscine-N-butylbromide (HBB) is used in gastrointestinal (GI) endoscopy to decrease motility and facilitate endoscopic procedures. Data from clinical studies to support this practice is limited especially for therapeutic procedures. Likewise, patterns of use among endoscopist are largely unclear. This study sought to assess usage of HBB among German-speaking endoscopists. Material and Methods We conducted an anonymous online survey among endoscopists in German-speaking countries. Results A total of 207 physicians participated in the survey. The majority (76.9%) were experienced endoscopists and 92.3% of respondents use HBB at least occasionally during procedures. The reported median stated frequency of HBB use varied greatly between different types of procedures and increased with the complexity of the procedure being performed. HBB was rarely used in diagnostic esophagogastroduodenoscopies (EGD) (median stated frequency 1% of procedures), while use frequency was significantly higher in EGD with endoscopic mucosal resection (EMR) (10%; p=0.002) and EGD with endoscopic submucosal dissection (ESD) (20%; p<0.001). Similarly, use frequency during diagnostic colonoscopy was lower (5%) compared to colonoscopy with EMR (20%, p=0.005) or ESD (42.5%, p<0.001). The highest use frequency was reported for ERCP (50%). The most frequently stated reason to use HBB was facilitation of the procedure (80.6%) followed by increasing diagnostic yield (58.3%). Conclusion German-speaking endoscopists commonly use HBB, most frequently to facilitate complex therapeutic procedures. Given there is almost no data supporting HBB use in therapeutic endoscopy, we suggest that more research is needed to evaluate benefits and risks of this practice.

Antibiotic prophylaxis and post-procedure infectious complications in endoscopic retrograde cholangiopancreatography with peroral cholangioscopy.

Background and study aims Single-operator peroral cholangioscopy (SOC) has gained increasing attention in modern biliary and pancreatic therapy and diagnosis. This procedure has shown higher rates of infectious complications than conventional endoscopic retrograde cholangiopancreatography (ERCP); therefore, many guidelines recommend antibiotic prophylaxis (AP). However, whether AP administration decreases infectious or overall adverse events (AEs) has been little studied. We aimed to study whether AP affects post-procedure infectious or overall AEs in ERCP with SOC. Patients and methods We collected data from the Swedish Registry for Gallstone Surgery and ERCP (GallRiks). Of the 124,921 extracted ERCP procedures performed between 2008 and 2021, 1,605 included SOC and represented the study population. Exclusion criteria were incomplete 30-day follow-up, ongoing antibiotic use, and procedures with unspecified indication. Type and dose of antibiotics were not reported. Post-procedure infectious complications and AEs at 30-day follow-up were the main outcomes. Results AP was administered to 1,307 patients (81.4%). In this group, 3.4% of the patients had infectious complications compared with 3.7% in the non-AP group. The overall AE rates in the AP and non-AP groups were 14.6% and 15.2%, respectively. The incidence of cholangitis was 3.1% in the AP group and 3.4% in the non-AP group. Using multivariable analysis, both infectious complications (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.54-1.57) and AEs (OR 0.87, 95% CI 0.65-1.16) remained unaffected by AP administration. Conclusions No reduction in infectious complication rates and AEs was seen with AP administration for SOC. The continued need for AP in SOC remains uncertain.

Epidemiology and treatment of renal anaemia in Spain: RIKAS retrospective study.

BACKGROUND AND OBJECTIVE: Studies on the prevalence of anaemia in chronic kidney disease in adults not on dialysis (CKD-ND) and in dialysis programmes (CKD-D) in Spain are not recent or focus on certain subgroups. The aim of this study was to know the epidemiology and current treatment patterns of anaemia associated with CKD in Spain. MATERIALS AND METHODS: Multicentre, non-interventional, retrospective study with CKD-ND stage 3a-5 and CKD-D patients treated in Spain between 2015 and 2017 (RIKAS study). RESULTS: The prevalence of anaemia in CKD-ND and CKD-D in 2015 was 33.8% and 91.5%, respectively, with similar results during 2016-2017. The prevalence of systemic inflammation in anaemic patients (18.1% and 51.8% for CKD-ND and CKD-D, respectively) was higher, especially in those treated with erythropoiesis-stimulating agents (ESA), compared to the general population with CKD-ND. After 12 months of follow-up, mean ferritin and transferrin saturation index (TSI) values in anaemic patients with CKD-ND were 187.1 ng/mL and 22.2%, respectively, while in CKD-D were 254.6 ng/mL and 20.2%. In ESA-treated patients, mean values were 190.6 ng/mL and 22.0% in ND-CKD, and 255.0 ng/mL and 20.2% in D-CKD. CONCLUSIONS: The prevalence of anaemia and inflammation increased with the disease severity, being higher in D-CKD. Iron parameters in anaemic patients treated or not with ESA are insufficient according to the guidelines, so there is room for improvement in the treatment of anaemia associated with CKD.

Impact of ERCP simulator training on early ERCP learning curves of novice trainees: a cohort study.

Background and study aim Simulator-based training has been extensively studied in training gastroduodenoscopy and colonoscopy and shown to significantly improve learning curves of novices. Data on simulator-based training in endoscopic retrograde cholangiopancreatography (ERCP) are scarce. We aimed to determine the impact of 2-day intensive hands-on simulator training on the course of the learning curve of novice trainees. Methods We conducted a prospective cohort study using a validated mechanical ERCP simulator (Boskoski-Costamagna ERCP Trainer). Six trainees were allocated to the simulation course program (SG). Each of these trainees were paired with an endoscopy trainee starting regular ERCP training at the same center who had no exposure to a simulation course program (control group; CG). The course included lectures, live ERCP demonstrations, and hands-on ERCP training to educate trainees in basic techniques related to cannulation, stent placement, stone extraction and stricture management. After the course, both the SG and CG started formal ERCP training in their respective centers. The Rotterdam Assessment Form for ERCP was used to register each performed ERCP. Simple moving average was applied to create learning curves based on successful common bile duct (CBD) cannulation. Outcomes were plotted against a historical cohort (HC). Results Thirteen trainees were included, six trainees in the SG and seven trainees in the CG, with a total of 717 ERCPs. Mean successful ERCP cannulation rate was higher for the simulator group at baseline compared to both CG and HC, 64% versus 43% and 42%, respectively. Differences became less explicit after 40 ERCPs, but persisted until a median of 75 ERCPs. Conclusions We demonstrate that 2-day hands-on simulator-based ERCP training course has a positive effect on the learning curves of ERCP trainees and should be considered an integral part of the training curricula for ERCP to develop skills prior to patient-based training.

Balloon enteroscopy-assisted endoscopic retrograde cholangiography and rendezvous procedures in patients with altered gastrointestinal anatomy.

BACKGROUND: Standard endoscopic retrograde cholangiography (ERC) frequently fails to treat biliary obstruction in patients with altered gastrointestinal anatomy. Balloon enteroscopy-assisted ERC (BE-ERC) and combined percutaneous transhepatic endoscopic rendezvous procedures (PTE-RVs) may offer effective rescue approaches. OBJECTIVE: This study aimed to evaluate the efficacy and safety of BE-ERC and PTE-RV for the treatment of biliary obstruction in patients with altered gastrointestinal anatomy. METHODS: In this observational study, all patients with altered gastrointestinal anatomy underwent BE-ERC between 2003 and 2016 at a tertiary referral center. In case of procedural failure, a combined PTE-RV was performed in selected cases. Endpoints included the success and safety of the procedures. RESULTS: A total of 180 BE-ERC performed in 106 patients with altered gastrointestinal anatomy were included. Of the procedures, 76.7% were performed due to benign and 23.3% due to malignant biliary obstruction. BE-ERC was successful in 53% (96/180) of cases. In case of failure, in 23/32 cases a combined PTE-RV was successfully performed, improving the overall success rate of BE-ERC, including PTE-RV, to 66% (119/180). Benign biliary obstruction and repeated procedures were positive predictors of successful BE-ERC (odds ratio 6.8 (95% CI 2.7-17.0), p < .001 and odds ratio 4.1 (2.1-8.2), p < .001). Complications were significantly more frequent in combined PTE-RVs than in BE-ERC procedures alone (34.4% vs. 7.4%; p < .001). CONCLUSIONS: BE-ERC is effective and safe for the endoscopic management of patients with altered gastrointestinal anatomy and percutaneous transhepatic rendezvous procedures can substantially increase success rates in selected cases.

Serum Levels of N- and C-ERC/Mesothelin and Clinicopathological Factors in Mesothelioma Patients and Those without Mesothelioma.

Objectives: ERC/mesothelin is a glycosylphosphatidylinositol (GPI)-anchor protein expressed in mesothelioma. A precursor protein is cleaved by proteases and an N-terminal fragment (N-ERC) is extracellularly secreted. A remaining C-terminal fragment (C-ERC) is tethered on cellular membranes by the GPI-anchor, but C-ERC is also released after cleavage by proteases. We and other groups reported that serum N-/C-ERC levels are associated with stages of mesothelioma and suggested the possibility of their usefulness as diagnostic markers. However, the N-ERC level is also influenced by renal functions that are not directly associated with conditions of mesothelioma. It is not known whether other clinical factors influence serum N-/C-ERC values. Furthermore, their relationship to the amount of ERC/Mesothelin in mesothelioma is not yet validated. The objective of this study is to clarify the relationship of serum N-/C-ERC levels and the status of mesothelioma and several clinical factors. Materials and Methods: We analyzed relations of serum N-/C-ERC levels and ages, gender and other clinical factors in 522 patients without mesothelioma and examined their relation to the amount of ERC/Mesothelin in mesothelioma tissues in 13 mesothelioma cases. Results: Serum N-ERC levels were influenced by renal functions. On the contrary, those of C-ERC were not influenced by any clinical factors examined in this study and were significantly correlated with the amount of ERC/Mesothelin in mesothelioma. Conclusion: Although both markers are good indicators of treatment-responses in individual patients with mesothelioma, only C-ERC reflected the amount of ERC/Mesothelin in mesothelioma among multiple patients, possibly because N-ERC was influenced by renal functions.

A Surgeon Involved in Basic Research - on the Occasion of Studying Abroad.

I, the author, expressed gratitude for receiving the 45th Juntendo Medical School Alumni Association Academic Encouragement Award in May 2023. After completing medical school and surgical training at Juntendo University, I embarked on a new challenge by pursuing a Ph.D. in basic clinical research, with a focus on gastric cancer, the third leading cause of cancer related death in Japan. Collaborating with various experts, I obtained a Ph.D. in cancer research studies in 2014. Subsequently, I pursued further research opportunities in the United States, where I undertook multiple projects focusing on cancer and maternal stress. I would like to present several studies, ERC/mesothelin, fatty acid synthase, and maternal stress in this manuscript. On returning to clinical practice at Juntendo University Shizuoka Hospital in 2019, I developed an interest in various clinical issues and decided to address these through experiments. In collaborating with several researchers at the Shizuoka Medical Research Center for Disasters, our ongoing research aims to answer several clinical questions. Furthermore, I aspire to guide junior staff in the future and am grateful for the invaluable connections and opportunities provided by Juntendo University.

A single centre experience of local perforator flaps in oncoplastic breast surgery; a cross-sectional study.

Background & objectives: Various oncoplastic techniques have emerged over the years to preserve breast cosmesis and symmetry without compromising the principles of tumor excision. One of the newer techniques for breast volume replacement to achieve symmetry and cosmesis is the use of fasciocutaneous pedicled chest wall perforator flaps or local perforator flaps (LPF). The objectives of this study were to document the details of the surgical procedure as well as patient-reported satisfaction and well-being following the procedure using a validated BREAST-Q tool among Pakistani women. Materials & methods: This cross-sectional study was conducted from March 2019 to February 2021 enrolling 25 female patients who underwent breast conservative surgery using LPF for breast tumors at The Aga Khan University Hospital, Karachi. Data related to the procedure was collected on a pre-designed proforma. Cosmetic outcomes and patient satisfaction were evaluated using 2 scales from BREAST-Q BCT domain version 2.0. The questionnaire was self-administered by the patients during their routine follow-up in the clinic. Data was analyzed using the Statistical Package for Social Sciences (SPSS) version 23. Mean (SD)/median (IQR) were computed for quantitative variables and frequency and percentages were calculated for qualitative variables. 2 sample t-test was applied. P-value ≤0.05 was considered significant. Results: 25 patients underwent LPF with a mean age of 47 ± 13.1 years. 8 LICAP, 7 AICAP, and 10 LTAP flaps were performed. Two postoperative complications of wound site erythema were encountered. 23 women were eligible for the BREAST-Q survey. Median (IQR) postoperative satisfaction with breasts and physical well-being chest (equivalent Rasch transformed score) was 100 (41) and 76 [18] respectively. We found high satisfaction with breasts and comparable physical well-being among Pakistani women after LPF surgeries. Conclusion: Local perforator flaps in oncoplastic breast-conserving surgery are a good option showing high satisfaction with breasts and physical well-being in Pakistani women.

Características y factores de riesgo de mortalidad por COVID-19 en Tamaulipas, a un año de pandemia / Characteristics and risk factors of COVID-19 mortality in Tamaulipas, one year after the pandemic

Resumen Coronavirus 19 (COVID-19), es una enfermedad viral prevalente y diseminada a nivel mundial, considerada una pandemia con alta tasa de mortalidad. A la fecha no existen estudios que describan la influencia de las variables asociadas a la enfermedad en el estado fronterizo de Tamaulipas, México. El objetivo del presente estudio fue evaluar y analizar las características, complicaciones, tasas de letalidad y factores de riesgo asociados a mortalidad en paciente positivos a COVID-19 en el estado de Tamaulipas, a un año de la emergencia local. Se utilizó la frecuencia de casos observados en relación a características, complicaciones y comorbilidades para estimar prevalencias y tasas de letalidad. Se ajustó un modelo de regresión logística multivariada para estimar los factores de riesgo significativos y se utilizaron curvas de supervivencia de Kaplan-Meier para describir las comorbilidades más importantes. Los análisis indicaron una mayor infección en pacientes en edad productiva, con una probabilidad significativa de muerte a partir de los 40 años, más evidente en pacientes masculinos. Los riesgos asociados a la hospitalización, como intubación endotraqueal y neumonía, son factores muy importantes. Las comorbilidades con alta prevalencia (diabetes, hipertensión y obesidad) y enfermedad renal crónica (ERC) están asociados significativamente (P < 0.01) a mayor mortalidad por COVID-19 en pacientes positivos. El presente estudio demostró algunos patrones generales de prevalencia y tasas de letalidad por COVID-19, por lo que se sugieren particularidades en los factores asociados a mortalidad en la población de Tamaulipas que requieren atención en sus grupos vulnerables, sobre todo en posibles casos de rebrotes de la enfermedad.

Abstract Coronavirus 19 (COVID-19) is a prevalent and globally disseminated viral disease that has become a pandemic associated with a high case fatality rate. To date, there are no published studies that describe the influence of the variables associated with the disease, specifically in the border state of Tamaulipas, Mexico. The objective of the present study was to assess the characteristics, complications, fatality rates and risk factors associated to mortality in patients positive to COVID-19 in Tamaulipas, one year after the local emergency. Descriptive frequency of characteristics, complications for prevalence and case fatality rates were used. A multivariate logistic regression model was adjusted to estimate the meaningful risk factors, and Kaplan-Meier survival curves were used to describe the most important comorbidities. The analysis indicated higher infection rates in patients of productive age, with a significant death probability in male patients from the age of 40. The risks associated with hospitalization, such as endotracheal intubation and the presence of pneumonia are important risk factors. Comorbidities with high prevalence; diabetes, hypertension, obesity, and chronic kidney disease (CKD) were significantly associated (P < 0.01) with higher COVID-19 mortality risk in the assessed population. The present study demonstrated some COVID-19 general patterns on frequency and mortality rates. It also suggested particularities in factors associated to mortality in the Tamaulipas population, which require proper attention in vulnerable groups, especially in future outbreaks of the disease.

Adynamic bone disease: Revisited.

The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.

Long-Term Outcomes of Endoscopic Management of Patients with Symptomatic Portal Cavernoma Cholangiopathy with No Shuntable Veins for Surgery or Failed Surgery.

Background and Aim: Shunt surgery is the definitive treatment for symptomatic patients with portal cavernoma cholangiopathy (PCC), but few patients are non-surgical candidates or fail to improve even after surgery. This study aims to analyze the long-term outcomes of endoscopic therapy in these patients. Methods: Retrospective review of a prospectively maintained database of all patients with symptomatic PCC managed with endoscopic retrograde cholangiography (ERC) followed by stent placement. Outcomes studied included number of biliary interventions, complications, resolution of stricture, development of decompensation and mortality. Results: Thirty-five patients (68.6% males, median age = 35 years) with a median follow-up duration of 46 months (12-112) were included in the analysis. Presentation was only jaundice in 51.4% cases while one-third (37.1%) of the patients presented with cholangitis. Patients underwent a total of 363 endoscopic sessions with a median of 9 procedures (3-29) per patient. Hemobilia was the most common complication of the procedure (6.06%). Ten (28.5%) patients required frequent stent exchanges. Patients who required frequent stent exchanges had higher number of cholangitis episodes and hospitalization. Secondary biliary cirrhosis developed in 4 (11.4%) patients and 2 (5.7%) patients had mortality. Of the 5 (14.3%) patients who were given a stent free trial, 3 patients required restenting due to redevelopment of symptoms. Conclusion: Patients with PCC without shuntable veins for surgery or those who failed to improve after surgery can be managed long-term with repeated endoscopic intervention with a slightly increased risk of non-fatal hemobilia.

A Prospective, Cohort Study of SITOIGANAP to Treat Glioblastoma When Given in Combination With Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Nivolumab or Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Pembrolizumab in Patients Who Failed Prior Treatment With Surgical Resection, Radiation, and Temozolomide.

Background: Glioblastoma (GBM) is the most common primary, malignant brain tumor in adults and has a poor prognosis. The median progression-free survival (mPFS) of newly diagnosed GBM is approximately 6 months. The recurrence rate approaches 100%, and the case-fatality ratio approaches one. Half the patients die within 8 months of recurrence, and 5-year survival is less than 10%. Advances in treatment options are urgently needed. We report on the efficacy and safety of a therapeutic vaccine (SITOIGANAP: Epitopoietic Research Corporation) administered to 21 patients with recurrent GBM (rGBM) under a Right-to-Try/Expanded Access program. SITOIGANAP is composed of both autologous and allogeneic tumor cells and lysates. Methods: Twenty-one patients with rGBM received SITOIGANAP on 28-day cycles in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), cyclophosphamide, bevacizumab, and an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody (either nivolumab or pembrolizumab). Results: The mPFS was 9.14 months, and the median overall survival (mOS) was 19.63 months from protocol entry. Currently, 14 patients (67%) are at least 6 months past their first SITOIGANAP cycle; 10 patients (48%) have received at least six cycles and have a mOS of 30.64 months and 1-year survival of 90%. The enrollment and end-of-study CD3+/CD4+ T-lymphocyte counts strongly correlate with OS. Conclusions: The addition of SITOIGANAP/GM-CSF/cyclophosphamide to bevacizumab and an anti-PD-1 monoclonal antibody resulted in a significant survival benefit compared to historic control values in rGBM with minimal toxicity compared to current therapy.

FGFR2-ERC1: A Subtype of FGFR2 Oncogenic Fusion Variant in Lung Adenocarcinoma and the Response to Anlotinib.

Background: Fibroblast growth factor receptor (FGFR) fusions in non-small cell lung cancer (NSCLC) are small genomic events. At present, there is no standard treatment strategy for patients with NSCLC carrying an FGFR fusion. Case Presentation: We report the case of a 45-year-old female patient who was diagnosed with lung adenocarcinoma and underwent right upper lobectomy and postoperative adjuvant chemotherapy. After 13 months, the patient's lung lesions progressed. Next-generation sequencing of venous blood and lung tissues confirmed an FGFR2-ERC1 fusion, and she received chemotherapy and immunotherapy. Two months later, the patient's lung lesions progressed again. Based on the target effect of anlotinib on FGFR, the patient was subsequently treated with anlotinib, and the progression-free survival interval exceeded 8.0 months. Conclusion: These findings showed that patients with lung adenocarcinoma carrying an FGFR2-ERC1 fusion gene may benefit from anlotinib. This case provided evidence to support the use of anlotinib in the treatment of NSCLC patients with FGFR fusion gene subtypes.

The Inhibitory Effects of Anti-ERC/Mesothelin Antibody 22A31 on Colorectal Adenocarcinoma Cells, within a Mouse Xenograft Model.

The expression of Renal Carcinoma (ERC)/mesothelin is enhanced in a variety of cancers. ERC/mesothelin contributes to cancer progression by modulating cell signals that regulate proliferation and apoptosis. Based on such biological insights, ERC/mesothelin has become a molecular target for the treatment of mesothelioma, pancreatic cancer, and ovarian cancer. Recent studies revealed about 50-60% of colorectal adenocarcinomas also express ERC/mesothelin. Therefore, colorectal cancer can also be a potential target of the treatment using an anti-ERC/mesothelin antibody. We previously demonstrated an anti-tumor effect of anti-ERC antibody 22A31 against mesothelioma. In this study, we investigated the effect of 22A31 on a colorectal adenocarcinoma cell line, HCT116. The cells were xenografted into BALB/c nu/nu mice. All mice were randomly allocated to either an antibody treatment group with 22A31 or isotype-matched control IgG1κ. We compared the volume of subsequent tumors, and tumors were pathologically assessed by immunohistochemistry. Tumors treated with 22A31 were significantly smaller than those treated with IgG1κ and contained significantly fewer mitotic cells with Ki67 staining. We demonstrated that 22A31 exhibited a growth inhibitory property on HCT116. Our results implied that ERC/mesothelin-targeted therapy might be a promising treatment for colorectal cancer.

Endoscopic Stone Extraction followed by Laparoscopic Cholecystectomy in Tandem for Concomitant Cholelithiasis and Choledocholithiasis: A Prospective Study.

BACKGROUND: Single-session endoscopic stone extraction (ESE) and laparoscopic cholecystectomy (LC) has the best outcome in managing concomitant cholelithiasis (gallstone disease [GSD]) and choledocholithiasis (common bile duct stone [CBDS]). Traditional rendezvous technique with an intraoperative cholangiogram is associated with various technical (bowel distention, frozen Calot's triangle, limitation of intraoperative cholangiogram and so on) and logistical difficulties (lack of trained personnel and equipment for ESE in the operating room). We modified our approach of ESE-LC (tandem ESE-LC) to study the safety of the approach and overcome these disadvantages of the traditional rendezvous approach. METHODS: A prospective study of patients with GSD and suspected CBDS from January 2017 to December 2019 was conducted. Tandem ESE-LC involves ESE and LC under the same general anaesthesia in a single day, while ESE is performed in the endoscopic suite using carbon dioxide insufflation, a balloon/basket was used for achieving bile duct clearance and the same was confirmed with an occlusion cholangiogram. Patients were then shifted to the operating room for LC. The primary outcome included bile duct clearance and safety of the procedure. RESULTS: Of 56 patients assessed for eligibility, 42 were included in the study (median age: 53 years, 25 [60%] women). Biliary colic was the most common presenting symptom (n = 24, 57%), followed by acute cholecystitis (n = 11, 26%). The median number of stones and stone size was 1 (1-6) and 4 mm (3-10), respectively. All patients had successful bile duct clearance. Stenting was performed in 5 (12%) patients. Intraoperatively, Calot's dissection was difficult and frozen in 10 and 11 patients respectively. The cystic duct was short and wide in 13 (31%) patients. Subtotal cholecystectomy was performed in 6 (14%) patients. The median duration of postprocedural hospital stay was 1 (0-13) day. Three patients had tandem ESE-LC on a day-care basis. One patient had post-endoscopic retrograde cholangiopancretography pancreatitis, and another required percutaneous drainage for gall bladder fossa collection. No patient had retained CBDS at a median follow-up of 18 (3-28) months. CONCLUSION: Tandem ESE-LC is safe and effective method in managing concomitant GSD and CBDS.